Mesenchymal factors play an important role in organ growth and differentiation. In the lung, a fibroblast factor has been shown to influence epithelial cell function in late fetal life, and we have shown morphologic evidence of close epithelial-mesenchymal cell contacts at this stage of development. The role of the various cell-cell interactions in modulating the normal patterns of proliferation and differentiated function of the different pulmonary cell types, before and after birth, is not known and is the subject of this investigation. Since the cellular contacts may be transient, we will examine and quantitate serially, mesenchymal junctions with undifferentiated Type 2 and Type 1 epithelium in developing rat lungs. Endothelial-mesenchymal junctions will be compared in different types of vessel. The frequency and type of intercellular contact will be correlated to division of specific cell types (3H thymidine autoradiography), to epithelial cell function (synthesis of saturated phospholipids) and to mesenchymal cell function (hydroxyproline synthesis). The importance of cell-cell interactions will also be assessed by studying the lung in conditions of altered development. For example steroids reduce epithelial proliferation and accelerate maturation before birth but their effects on division and function of other cell types and on cell-cell interactions before and after birth are not known and will now be studied. An inhibitor of collagen synthesis will be injected to study the role of the fibroblastic activity on cell contacts and the developmental process. Although the principal goal will be the understanding of cellular events in development, the study has relevance to the patterns of cellular renewal following injury, which usually recapitulates the developmental process. The results of the proposed investigation will be correlated with a study on cellular interdependence during injury and repair that is underway at present in our laboratory. These initial steps in establishing links between cell-cell interactions and cell division and function are essential before pursuing the identity of the message or messenger molecules, and the subsequent manipulation of the system in situations of abnormal development or abnormal repair of the lung.